Tegmental cholinergic neurons vary their discharge patterns across the sleep-wake cycle, and glutamate is suggested to play an important role in determining these firing patterns. Cholinergic and noncholinergic neurons in the mesopontine tegmentum have different susceptibilities to various excitotoxins, presumably because of heterogeneity in the expression of glutamate receptor subtypes in this area. By using a double-labeling procedure that combines nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) histochemistry and avidin-biotin-peroxidase immunocytochemistry with diaminobenzidine as the chromogen, we compared the colocalization of AMPA receptor subunits GluR1, GluR2/3, and GluR4, kainate receptor subunits GluR5/6/7, and an NMDA receptor subunit NMDAR1 on NADPH-diaphorase-positive (cholinergic) neurons in the mesopontine tegmentum. Throughout the brainstem, neurons immunoreactive for GluR2/3 and NMDAR1 were most numerous, whereas neurons labeled for GluR1, GluR4, and GluR5/6/7 were less common. Specifically within the mesopontine tegmentum, the proportion of double-labeled neurons in the diaphorase-containing cell population was highest with GluR1 (43%) and lowest with GluR5/6/7 (12%). Regardless of the receptor subunit type, the greatest numbers of double-labeled neurons were observed in the pedunculopontine tegmental nucleus pars compacta and the fewest in the dorsal aspect of the laterodorsal tegmental nucleus. In addition, there were regional differences in the relative expression of receptor subunits and diaphorase-positive neurons across the subdivisions of the tegmental cholinergic column. Because each ionotropic subunit confers distinctive properties to a receptor channel, the present results suggest that mesopontine cholinergic neurons have nonuniform responses to glutamate and are also discriminable from basal forebrain cholinergic neurons in terms of glutamate receptor configuration.
The role of the pedunculopontine tegmental nucleus (PPTg) in stimulus-reward learning was assessed by testing the effects of PPTg lesions on performance in visual autoshaping and conditioned reinforcement (CRf) paradigms. Rats with PPTg lesions were unable to learn an association between a conditioned stimulus (CS) and a primary reward in either paradigm. In the autoshaping experiment, PPTg-lesioned rats approached the CS+ and CS- with equal frequency, and the latencies to respond to the two stimuli did not differ. PPTg lesions also disrupted discriminated approaches to an appetitive CS in the CRf paradigm and completely abolished the acquisition of responding with CRf. These data are discussed in the context of a possible cognitive function of the PPTg, particularly in terms of lesion-induced disruptions of attentional processes that are mediated by the thalamus.
The role of the pedunculopontine tegmental nucleus (PPTg) in the control of behaviour is investigated in the experiments in this thesis through (1) the interactions between its ascending cholinergic neurones and dopamine neurones in the substantia nigra and ventral tegmental area; and (2) the involvement of its non- cholinergic neurones in modifying outflow from the striatum. (1) Stimulation of rat SN by carbachol produces an increase in behaviours for which the animal has a low current baseline rate and a positive predisposition (Winn et al, 1983). This was investigated further by examining first, whether consumption of a palatable food could also be stimulated by intranigral injections of nicotine or acetylcholinesterase inhibitors. Increased feeding was obtained dose- dependently from satiated rats following injection of carbachol, nicotine or neostigmine, but not eserine, into the substantia nigra. Second, it was demonstrated that spontaneous consumption by satiated rats could not be blocked by muscarinic or nicotinic antagonists, although eating stimulated by intranigral neostigmine were attenuated by these antagonists. These data suggest that the cholinergic innervation of substantia nigra is phasic in nature. Third, it was ascertained whether the excitation realised by neostigmine injections into the substantia nigra or ventral tegmental area could support the acquisition of responding for conditioned reinforcement. Injections of neostigmine into the substantia nigra, but not ventral tegmental area, assisted acquisition of the lever-press response and this resuh is discussed with respect to the significance of habit and expectation on responding. (2) The PPTg has been viewed as an important striatal output station for several years, primarily due to its proposed function as part of the mesencephalic locomotor region but more recently for its role in incentive behaviours. The validity of these perspectives was tested first by investigating the effects of ibotenate PPTg lesions on the well-known pattern of events which occur following systemic injections of d-amphetamine and apomorphine. The effects of lesions made in the deep mesencephalic nucleus were also investigated as this structure has also been linked with locomotor functions. Neither spontaneous nor drug-induced locomotion was affected by either lesion placement, but PPTg-lesioned rats exhibited abnormal stereotypies. At 3.0 and 5.0 mg-kg-1 d-amphetamine these included excessive biting behaviour, predominantly directed at their own forepaws, and they were the only group to score 6 (continuous biting) on the Creese-Iversen scale following apomorphine injections. The role of the PPTg in the mediation of reward-related behavior was investigated in the conditioned reinforcement paradigm. Ibotenate-lesioned rats responded as frequently as controls on the CR lever, but their pressing was equal on CR and NCR levers. These data are discussed with respect to a role for the non-cholinergic neurones in the PPTg in the mediation of stimulus-reward associations and…
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